This proposal aims at characterizing the structural and functional properties of the gene products of the various loci of the human I region and at identifying the corresponding receptors on alloactivated T cells. Human and murine monoclonal antibodies to distinct domains of Ia antigens will be developed using several immunization procedures and characterized with a combination of serological and immunochemical assays. Antibodies will be used to analyze the molecular organization of the gene products of the I region and the structural relationship among the antigenic series identified with alloantisera in the Ia system. Antibodies will be used to probe the function of distinct domains of Ia antigens in cell-cell interactions. The clinical significance of these findings will be assessed by determining the association between determinants recognized by monoclonal antibodies and susceptibility to disease. Monoclonal antibodies to Ia allospecificities will be used to elicit antiidiotypic xenoantisera and monoclonal antibodies. These reagents will be evaluated for their effect on cell-cell interactions and to quantitate alloreactive T cells in subjects exposed to the appropriate Ia allospecificity. The clinical significance of this approach will be assessed by correlating the number of alloreactive T cells in kidney allograft recipients with the clinical course of the disease. Antiidiotype antibodies may eventually be used to manipulate specific immune responses in organ transplantation.